ABSTRACT Despite recognition that the US opioid epidemic1,2 is due, in part, to diversion of legally obtained prescriptions by individuals other than the intended user,3,4 opioids are still frequently prescribed in excess after surgery and accounted for 9.8% of all opioid prescriptions filled in 2012.5 However, approximately 80% of the pills within the 28.3 million prescriptions written by a surgical provider go unused, leaving a staggering number of pills available for diversion.5,6 This study will implement evidence-based practices using a multi- faceted intervention throughout the Northwestern Medicine network of hospitals to (a) decrease prescribed opioid analgesics following surgery while (b) assuring adequate post-surgery patient-reported pain related outcomes. The multi-faceted intervention includes: [1] electronic health record (EHR)-based decision support tools; [2] prescriber education; [3] standardized patient education materials; and [4] automated provision of prior opioid prescription information through the Illinois Prescription Monitoring Program (IL-PMP). The existing surgical quality implementation teams (Surgeon, Quality Improvement Expert, Data Abstractor), in collaboration with an Anesthesiologist, a Pharmacist, and an electronic medical record (EMR) Programmer at each hospital will create the system-specific contextual, multi-component intervention to support adherence to evidence-based best practices. Four surgical specialties (General, Orthopedics, Urology, and Gynecology at each hospital) at four diverse hospitals (1 academic, 2 large community, and 1 small community hospital) will adapt the intervention to address system-specific contextual factors for implementation at their institution. The Electronic Data Warehouse (EDW) will be leverage to monitor the effect of the intervention on prescriptions written on discharge from surgical encounters, and NM Pro will be utilized to collect pain-related patient reported outcomes throughout the study period. The five domains of the Consolidated Framework for Implementation Research (CFIR) will be used to guide the implementation with a focus on identifying and documenting the system-specific contextual factors and strategies, used by the hospital implementation teams to facilitate systems-level change within each healthcare system to promote broad use of evidence-based best practices. This study will provide both conceptual and practical advances for implementation of an intervention to support adherence to best practices in diverse healthcare systems, which should enable efficient implementation throughout the Illinois Surgical Quality Improvement Collaborative (ISQIC), a well-established 56 hospital learning collaborative, led by our research team, and will be applicable to the diverse hospitals across the United States.